Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Clostridium difficile-associated disease in human stem cell transplant recipients: coming epidemic or false alarm?

Bone Marrow Transplantation volume 42, pages 705–713 (2008)Cite this article

Abstract

Clostridium difficile is the most common cause of nosocomial diarrhea in the United States and Europe, and is a cause of significant morbidity and mortality among hospitalized patients. A newly identified epidemic strain has been associated with many hospital outbreaks of C. difficile-associated disease (CDAD), raising the concern of an escalating burden of CDAD among at-risk patients. Hematopoietic SCT (HSCT) recipients are known to be at increased risk for a wide variety of infectious complications, including CDAD as a result of prolonged hospitalizations, exposure to broad-spectrum antibiotics, altered integrity of the intestinal mucosa and GVHD. The incidence of CDAD in the HSCT population has been reported as high as 20% in some large series. The frequency and seriousness of CDAD in this defined group as compared with the general hospital population, however, are not clearly delineated. We discuss the epidemiology and diagnosis of CDAD and review recent studies examining the risk factors and characteristics of CDAD in HSCT recipients. Finally, we provide a management algorithm for the diagnosis and treatment of CDAD at our institution.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

Article 08 April 2021

Antoni Torres, Catia Cilloniz, … Tom van der Poll

References

  1. Cloud J, Kelly CP . Update on Clostridium difficile associated disease. Curr Opin Gastroenterol 2007; 23: 4–9.

    PubMed  Google Scholar 

  2. Owens Jr RC, Valenti AJ . Clostridium difficile-associated disease in the new millennium: ‘the perfect storm’ has arrived. Infect Dis Clin Pract 2007; 15: 299–315.

    Article  Google Scholar 

  3. Blossom DB, McDonald LC . The challenges posed by reemerging Clostridium difficile infection. Clin Infect Dis 2007; 45: 222–227.

    Article  PubMed  Google Scholar 

  4. Missaghi B, Valenti AJ, Owens Jr RC . Clostridium difficile infection: a critical overview. Curr Infect Dis Rep 2008; 10: 165–173.

    Article  PubMed  Google Scholar 

  5. Monaghan T, Boswell T, Mahida YR . Recent advances in Clostridium difficile-associated disease. Gut 2008; 57: 850–860.

    CAS  PubMed  Google Scholar 

  6. McDonald LC, Killgore GE, Thompson A, Owens Jr RC, Kazakova SV, Sambol SP et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med 2005; 353: 2433–2441.

    Article  CAS  PubMed  Google Scholar 

  7. Loo VG, Poirier L, Miller MA, Oughton M, Libman MD, Michaud S et al. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 2005; 353: 2442–2449.

    Article  CAS  PubMed  Google Scholar 

  8. Bartlett JG . Narrative review: the new epidemic of Clostridium difficile-associated enteric disease. Ann Intern Med 2006; 145: 758–764.

    Article  PubMed  Google Scholar 

  9. Owens RC . Clostridium difficile-associated disease: changing epidemiology and implications for management. Drugs 2007; 67: 487–502.

    Article  CAS  PubMed  Google Scholar 

  10. McMaster-Baxter NL, Musher DM . Clostridium difficile: recent epidemiologic findings and advances in therapy. Pharmacotherapy 2007; 27: 1029–1039.

    Article  CAS  PubMed  Google Scholar 

  11. McFarland LV . Update on the changing epidemiology of Clostridium difficile-associated disease. Nat Clin Pract Gastroenterol Hepatol 2008; 5: 40–48.

    Article  PubMed  Google Scholar 

  12. Jank T, Giesemann T, Aktories K . Rho-glucosylating Clostridium difficile toxins A and B: new insights into structure and function. Glycobiology 2007; 17: 15R–22R.

    Article  CAS  PubMed  Google Scholar 

  13. Genth H, Dreger SC, Huelsenbeck J, Just I . Clostridium difficile toxins: more than mere inhibitors of Rho proteins. Int J Biochem Cell Biol 2008; 40: 592–597.

    Article  CAS  PubMed  Google Scholar 

  14. Bobak DA . The molecular pathogenesis of Clostridium difficile-associated disease. Curr Infect Dis Rep 2008; 10: 111–115.

    Article  PubMed  Google Scholar 

  15. Bustelo XR, Sauzeau V, Berenjeno IM . GTP-binding proteins of the Rho/Rac family: regulation, effectors and functions in vivo. Bioessays 2007; 29: 356–370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Vega FM, Ridley AJ . Rho GTPases in cancer cell biology. FEBS Lett 2008; 582: 2093–2101.

    Article  CAS  PubMed  Google Scholar 

  17. Yolken RH, Bishop CA, Townsend TR, Bolyard EA, Bartlett J, Santos GW et al. Infectious gastroenteritis in bone-marrow transplant recipients. N Engl J Med 1982; 306: 1010–1012.

    Article  CAS  PubMed  Google Scholar 

  18. Cox GJ, Matsui SM, Lo RS, Hinds M, Bowden RA, Hackman RC et al. Etiology and outcome of diarrhea after marrow transplantation: a prospective study. Gastroenterology 1994; 107: 1398–1407.

    Article  CAS  PubMed  Google Scholar 

  19. Mossad SB, Longworth DL, Goormastic M, Serkey JM, Keys TF, Bolwell BJ . Early infectious complications in autologous bone marrow transplantation: a review of 219 patients. Bone Marrow Transplant 1996; 18: 265–271.

    CAS  PubMed  Google Scholar 

  20. Yuen KY, Woo PC, Liang RH, Chiu EK, Chen FF, Wong SS et al. Clinical significance of alimentary tract microbes in bone marrow transplant recipients. Diagn Microbiol Infect Dis 1998; 30: 75–81.

    Article  CAS  PubMed  Google Scholar 

  21. Bilgrami S, Feingold JM, Dorsky D, Edwards RL, Bona RD, Khan AM . Incidence and outcome of Clostridium difficile infection following autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 1999; 23: 1039–1042.

    Article  CAS  PubMed  Google Scholar 

  22. Avery R, Pohlman B, Adal K, Bolwell B, Goldman M, Kalaycio M et al. High prevalence of diarrhea but infrequency of documented Clostridium difficile in autologous peripheral blood progenitor cell transplant recipients. Bone Marrow Transplant 2000; 25: 67–69.

    Article  CAS  PubMed  Google Scholar 

  23. Chakrabarti S, Lees A, Jones SG, Milligan DW . Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality. Bone Marrow Transplant 2000; 26: 871–876.

    Article  CAS  PubMed  Google Scholar 

  24. van Kraaij MG, Dekker AW, Verdonck LF, van Loon AM, Vinjé J, Koopmans MP et al. Infectious gastro-enteritis: an uncommon cause of diarrhoea in adult allogeneic and autologous stem cell transplant recipients. Bone Marrow Transplant 2000; 26: 299–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Barton T, Collis T, Stadtmauer E, Schuster M . Infectious complications the year after autologous bone marrow transplantation or peripheral stem cell transplantation for the treatment of breast cancer. Clin Infect Dis 2001; 32: 391–395.

    Article  CAS  PubMed  Google Scholar 

  26. Gorschlüter M, Glasmacher A, Hahn C, Schakowski F, Ziske C, Molitor E et al. Clostridium difficile infection in patients with neutropenia. Clin Infect Dis 2001; 33: 786–791.

    Article  PubMed  Google Scholar 

  27. Tomblyn M, Gordon L, Singhal S, Tallman M, Williams S, Winter J et al. Rarity of toxigenic Clostridium difficile infections after hematopoietic stem cell transplantation: implications for symptomatic management of diarrhea. Bone Marrow Transplant 2002; 30: 517–519.

    Article  CAS  PubMed  Google Scholar 

  28. Jillella AP, Ustun C, Robach E, Sertkaya D, DiPiro C, Kallab AM et al. Infectious complications in patients receiving mobilization chemotherapy for autologous peripheral blood stem cell collection. J Hematother Stem Cell Res 2003; 12: 155–160.

    Article  CAS  PubMed  Google Scholar 

  29. Arango JI, Restrepo A, Schneider DL, Callander NS, Ochoa-Bayona JL, Restrepo MI et al. Incidence of Clostridium difficile-associated diarrhea before and after autologous peripheral blood stem cell transplantation for lymphoma and multiple myeloma. Bone Marrow Transplant 2006; 37: 517–521.

    Article  CAS  PubMed  Google Scholar 

  30. Balagopal A, Sears CL . Clostridium difficile: new therapeutic options. Curr Opin Pharmacol 2007; 7: 455–458.

    Article  CAS  PubMed  Google Scholar 

  31. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB . A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis 2007; 45: 302–307.

    Article  CAS  PubMed  Google Scholar 

  32. Kuijper EJ, Wilcox MH . Decreased effectiveness of metronidazole for the treatment of Clostridium difficile infection? Clin Infect Dis 2008; 47: 63–65.

    Article  PubMed  Google Scholar 

  33. Al-Nassir WN, Sethi AK, Nerandzic MM, Bobulsky GS, Jump RL, Donskey CJ . Comparison of clinical and microbiological response to treatment of Clostridium difficile-associated disease with metronidazole and vancomycin. Clin Infect Dis 2008; 47: 56–62.

    Article  PubMed  Google Scholar 

  34. Bartlett JG . The case for vancomycin as the preferred drug for treatment of Clostridium difficile infection. Clin Infect Dis 2008; 46: 1489–1492.

    Article  CAS  PubMed  Google Scholar 

  35. Gerard L, Garey KW, DuPont HL . Rifaximin: a nonabsorbable rifamycin antibiotic for use in nonsystemic gastrointestinal infections. Expert Rev Anti Infect Ther 2005; 3: 201–211.

    Article  CAS  PubMed  Google Scholar 

  36. Garey KW, Salazar M, Shah D, Rodrigue R, DuPont HL . Rifamycin antibiotics for treatment of Clostridium difficile-associated diarrhea. Ann Pharmacother 2008; 42: 827–835.

    Article  CAS  PubMed  Google Scholar 

  37. Bobak DA . Use of nitazoxanide for gastrointestinal tract infections: treatment of protozoan parasitic infection and beyond. Curr Infect Dis Rep 2006; 8: 91–95.

    Article  PubMed  Google Scholar 

  38. Musher DM, Logan N, Hamill RJ, Dupont HL, Lentnek A, Gupta A et al. Nitazoxanide for the treatment of Clostridium difficile colitis. Clin Infect Dis 2006; 43: 421–427.

    Article  CAS  PubMed  Google Scholar 

  39. Musher DM, Logan N, Mehendiratta V, Melgarejo NA, Garud S, Hamill RJ . Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide. J Antimicrob Chemother 2007; 59: 705–710.

    Article  CAS  PubMed  Google Scholar 

  40. Maroo S, Lamont JT . Recurrent Clostridium difficile. Gastroenterology 2006; 130: 1311–1316.

    Article  PubMed  Google Scholar 

  41. Bobak DA . Clinical Trials Report: nitazoxanide to treat persistent Clostridium difficile colitis. Curr Infect Dis Rep 2008; 10: 89–90.

    Article  PubMed  Google Scholar 

  42. Bobak DA . Clinical Trials Report: rifaximin to treat recurrent Clostridium difficile colitis. Curr Infect Dis Rep 2008; 10: 90–91.

    Google Scholar 

  43. Johnson S, Schriever C, Galang M, Kelly CP, Gerding DN . Interruption of recurrent Clostridium difficile-associated diarrhea episodes by serial therapy with vancomycin and rifaximin. Clin Infect Dis 2007; 44: 846–848.

    Article  CAS  PubMed  Google Scholar 

  44. Sebaihia M, Wren BW, Mullany P, Fairweather NF, Minton N, Stabler R et al. The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome. Nat Genet 2006; 38: 779–786.

    Article  PubMed  Google Scholar 

  45. Carling PC, Parry MF, Von Beheren SM . Identifying opportunities to enhance environmental cleaning in 23 acute care hospitals. Infect Control Hosp Epidemiol 2008; 29: 1–7.

    Article  CAS  PubMed  Google Scholar 

  46. Dellit TH, Owens RC, McGowan Jr JE, Gerding DN, Weinstein RA, Burke JP et al. Infectious Diseases Society of America sand the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007; 44: 159–177.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland, OH, USA

    D Bobak, L M Arfons, R J Creger & H M Lazarus

  2. Department of Medicine, The Ireland Cancer Center, University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland, OH, USA

    L M Arfons, R J Creger & H M Lazarus

Authors
  1. D Bobak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L M Arfons
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R J Creger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H M Lazarus
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Bobak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bobak, D., Arfons, L., Creger, R. et al. Clostridium difficile-associated disease in human stem cell transplant recipients: coming epidemic or false alarm?. Bone Marrow Transplant 42, 705–713 (2008). https://doi.org/10.1038/bmt.2008.317

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.317

Keywords

This article is cited by

Search

Advanced search

Quick links